Harada H, Ishizaka A, Yonemaru M, Mallick A A, Hatherill J R, Zheng H, Lilly C M, O'Hanley P T, Raffin T A
Department of Medicine, Stanford University Medical Center, CA 94305-5204.
Am Rev Respir Dis. 1989 Oct;140(4):974-80. doi: 10.1164/ajrccm/140.4.974.
We studied the effects of the methylxanthines, aminophylline (AMPH) and pentoxifylline (PTXF), on multiple organ damage following Escherichia coli sepsis in guinea pigs. To assess multiple organ damage, 125I-labeled albumin accumulation was measured in bronchoalveolar lavage (BAL) fluid, lung, kidneys, liver, heart, adrenal glands, and spleen and expressed as a ratio of BAL fluid or tissue to 125I-labeled albumin plasma (albumin index: Al). Wet-to-dry lung weight (W/D) ratios were also measured. The methylxanthines were administered by a bolus injection followed by a continuous infusion. The seven experimental groups included: saline-control, AMPH-control, PTXF-control, E. coli septic-control, E. coli septic-AMPH high dose, E coli septic-AMPH low dose, and E. coli septic-PTXF. The AI of the BAL fluid and all examined organs significantly increased in the septic-control group compared to those in the saline-, AMPH-, and PTXF-control groups, In all septic-methylxanthine groups, the AI of the BAL fluid and all organs, except for the spleen, were significantly lower than those of the septic-control group. Compared to the saline-, AMPH-, and PTXF-control groups, the septic-control group revealed a significant increase in lung W/D ratios, whereas the septic-AMPH high and low dose groups and the septic-PTXF group did not. Of importance, the septic-PTXF group did not cause a significant decrease in mean arterial pressure (MAP) as compared to the control groups, whereas the septic-AMPH groups did cause a significant decrease in MAP compared to the septic-control group. Therefore, the data from this experiment demonstrate that both AMPH and PTXF attenuate the multiple organ albumin leak seen in septic guinea pigs. However, PTXF exerted this protective effect with no discernible effect on the MAP whereas the MAP of AMPH-treated guinea pigs was significantly decreased.
我们研究了甲基黄嘌呤、氨茶碱（AMPH）和己酮可可碱（PTXF）对豚鼠大肠杆菌败血症后多器官损伤的影响。为评估多器官损伤，我们测定了支气管肺泡灌洗（BAL）液、肺、肾、肝、心脏、肾上腺和脾脏中125I标记白蛋白的蓄积量，并将其表示为BAL液或组织与125I标记白蛋白血浆的比值（白蛋白指数：Al）。还测量了肺湿重与干重（W/D）比值。甲基黄嘌呤通过静脉推注给药，随后持续输注。七个实验组包括：生理盐水对照组、AMPH对照组、PTXF对照组、大肠杆菌败血症对照组、大肠杆菌败血症-AMPH高剂量组、大肠杆菌败血症-AMPH低剂量组和大肠杆菌败血症-PTXF组。与生理盐水对照组、AMPH对照组和PTXF对照组相比，败血症对照组中BAL液和所有检测器官的Al显著升高。在所有败血症-甲基黄嘌呤组中，BAL液和除脾脏外所有器官的Al均显著低于败血症对照组。与生理盐水对照组、AMPH对照组和PTXF对照组相比，败血症对照组的肺W/D比值显著升高，而败血症-AMPH高剂量组、低剂量组和败血症-PTXF组则没有。重要的是，与对照组相比，败血症-PTXF组并未导致平均动脉压（MAP）显著降低，而败血症-AMPH组与败血症对照组相比确实导致MAP显著降低。因此，本实验数据表明，AMPH和PTXF均可减轻败血症豚鼠出现的多器官白蛋白渗漏。然而，PTXF发挥这种保护作用时对MAP无明显影响，而AMPH处理的豚鼠的MAP则显著降低。
